Bacterial infections are responsible for diseases or syndromes such as urinary tract infection, skin and soft tissue infection, sexually transmitted infection, tetanus, typhoid, tuberculosis, cholera, syphilis, pneumonia or salmonella. Despite the high number and the diversity of antibacterial agents, bacterial infections are a main cause of death worldwide, especially in developing countries. Moreover, the continuous appearance of drug-resistant bacteria is worrying both in developed and developing countries.
The over-prescription of antibiotics seems to be one of the main reasons of the appearance of resistances. However, other factors such as the use of antibiotics in animal husbandry and the increasing number of antibacterial agents in cleaning products are also responsible for the appearance of resistance. Moreover, even without exposure to antibiotics, DNA mutations and acquisition of extra chromosomic DNA naturally occur in bacteria potentially leading to resistance.
Depending on their degree of resistance, drug-resistant bacteria are classified in three groups: multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) (Magiorakos, A.-P. et al, Clinical Microbiology and Infection, 2012, pp. 268-281). There is thus a need to develop antibiotics active against wild type of bacteria but also against the different classes of drug-resistant bacteria. Moreover, any bacteria that survive exposure to an antibiotic will replicate and produce resistance offspring and antibiotics have thus to possess a maximal capability of bacterial eradication.
Quinolones form a large class of antibiotics developed in the 60s possessing activities against a broad scope of bacteria. The addition of a fluorine atom on the aromatic ring led to the discovery, in the 70s, of fluoroquinolones. These molecules possess improved pharmacokinetic properties compared to quinolones such as good oral absorption, good tissue penetration and relatively long duration of activity. Fluoroquinolones such as ciprofloxacin (U.S. Pat. No. 4,670,444, EP0049355), enrofloxacin (U.S. Pat. No. 4,670,444, EP0049355), gatifloxacin (U.S. Pat. No. 4,980,470) and moxifloxacin (U.S. Pat. No. 5,607,942) are currently used to treat various types of bacterial infections that is as initial treatment or second-line therapy.

The mechanism of action of fluoroquinolone in bacteria consists in inhibiting the bacterial enzyme DNA gyrase necessary for DNA replication and resistance to fluoroquinolone mainly comes from mutation on DNA gyrase.
Therefore, even if fluoroquinolones allow to treat a large scope of bacterial infections and possess good pharmacokinetics properties, these molecules suffer from the appearance of high resistance.
There is thus a need to develop new compounds active against wild-type of bacteria but also against drug-resistant bacteria that is MDR, XDR or PDR. Such compounds have to be capable of overcoming the resistance mechanisms developed by bacteria against currently used antibiotics and have to possess a maximal capability of bacterial eradication while exhibiting a low toxicity.
The present invention relates to compounds of the class of fluoroquinolones possessing a piperazine moiety substituted by a long alkyl chain. The compounds of the invention possess an improved bactericidal activity compared to currently used fluoroquinolones against wild-type bacteria but also against drug-resistant bacteria.